The increasing demand to produce enantiomerically pure pharmaceuticals, agrochemicals, flavors, and other fine chemicals has advanced the field of asymmetric catalytic technologies. Development of efficient asymmetric metal-catalyzed transformations has played a central role for the advancement of asymmetric catalysis (Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds., Comprehensive Asymmetric Catalysis, Springer, Berlin, 1999; Ojima, I., Ed, Catalytic Asymmetric Synthesis, VCH, New York, 1993; and Noyori, R. Asymmetric Catalysis In Organic Synthesis, John Wiley & Sons, Inc., New York, 1994). Among most successful transformations are asymmetric hydrogenation, asymmetric epoxidation and dihydroxylations, which were awarded Nobel Prizes in 2001 for their efficiency, simplicity, and practicality. Chiral ligand design has become and will continue to be of great importance for developing new efficient asymmetric metal-catalyzed reactions.
Asymmetric hydrogenation utilizing molecular hydrogen to reduce prochiral olefins, ketones, and imines has become one of most efficient methods for constructing chiral compounds. It also accounts for the major asymmetric catalytic transformation at commercial scales. Development of efficient chiral phosphorus ligands is essential for the success of asymmetric hydrogenation. Known chiral phosphorus ligands in this field include Knowles' DIPAMP [Knowles, W. S. Acc. Chem. Res. 1983, 16, 106], Kagan's DIOP [Kagan et al, J. Am. Chem. Soc. 1972, 94, 6429], Noyori's BINAP [Noyori, R. Chem. Soc. Rev. 1989, 18, 187], Burk's Duphos and BPE [Burk, M. J. et al, Organometallics 1990, 9, 2653; Burk, M. J. et al, Angew. Chem., Int. Ed. Engl. 1990, 29, 1462], Imamoto's BisP* [Imamoto, T. et al, J. Am. Chem. Soc. 1997, 119, 1799], Zhang's PennPhos [Zhang, X. et al, Angew. Chem. Int. Ed. Engl. 1999, 38, 516] and TangPhos [US2004/0229846 and Zhang, X. et al, Angew. Chem. Int. Ed. 2002, 41, 1613.], Pfizer's trichickenfootphos [WO2005/087370 and Hoge, G. et al, J. Am. Chem. Soc. 2004, 126, 5966].
Recently, we described a novel series of BIBOP and POP ligands which were derived from a rigid modular P-chiral dihydrobenzooxaphosphole core, in WO 2011/056737. These ligands showed high enantioselectivity in Rhodium catalyzed asymmetric hydrogenation of functionalized olefins, such as enamides and amino acids.
Although tremendous progress has been made in the field of asymmetric hydrogenation and many efficient chiral ligands have been developed, the design of new efficient ligands continues to be important since there is no universal ligand for hydrogenation of various kinds of prochiral substrates.